The goal of this STTR application is to develop 123I- and 99Tc-labeled labeled sigma-1 (sigma1) receptor imaging agents for Single Photon Emission Computed Tomography (SPECT) studies of solid tumors. This approach is based on the observation that sigma1 receptors are expressed in high density in a number of human tumors and are a suitable target for radiotracer development. Our preliminary data also indicate that SPECT- based sigma1 receptor imaging agents may also provide information regarding the proliferative status of solid tumors. An additional incentive for focusing on sigma1 receptors stems from our development of sigma1- selective compound, N-benzyl-4-yl phenylacetamide, that will serve as the lead compound for SPECT radiotracer development. The strategy for introducing 123I will be to incorporate an iodine atom into a region of the lead compound that does not result in a reduction in affinity for sigma1 receptors. The second year of this Phase I grant will address the feasibility of preparing a high affinity sigma1 receptors imaging agent containing a 99m/Tc-complex. Although the proposed radiopharmaceuticals will initially benefit the diagnosis and treatment of breast cancer, we believe the technology developed in this STTR application will translated to other human cancers that posses a high density of sigma1 receptors. PROPOSED COMMERCIAL APPLICATIONS: The radiopharmaceuticals developed from this STTR application have a high commercialization potential since they will use a nuclear medicine imaging procedure (SPECT IMAGING) having a widespread availability. The imaging strategy described in this application could provide a useful clinical tool for both the diagnosis, treatment strategy, and therapeutic monitoring of cancer patients.